The long-term survival of histoincompatible canine lung transplants has been achieved following treatment with total-body irradiation, autologous bone marrow reconstitution and short-term methotrexate administration. The objectives of the proposed research are to study the cellular immune mechanisms of the canines which have functioning nonidentical lung allografts and to monitor changes in immune reactivities of future transplant recipients. The mixed lymphocyte culture assay, the cell mediated lympholysis assay, the lymphocyte mediated cytotoxicity assay and the antibody dependent cell mediated cytotoxicity assay will be established and used to measure the reactivity of recipient mononuclear cells to donor antigens. In addition to these in vitro assays, skin grafts from the donors and third party animals will be applied to the recipients in an attempt to determine the specificity of the tolerant state in vivo. In studying the reactivity of recipient cells to donor antigens, the mechanisms required for the induction of a state of specific tolerance would be more clearly defined. Further knowledge of the mechanisms involved in allograft tolerance would have major clinical implications in human organ transplantation and could lead to improvements in the specific manipulation of these processes.